Threonine-rich carboxyl-terminal extension drives aggregation of stalled polypeptides.

Ribosomes translating damaged mRNAs may stall and prematurely split into their large and small subunits. The split large ribosome subunits can continue elongating stalled polypeptides. In yeast, this mRNA-independent translation appends the C-terminal alanine/threonine tail (CAT tail) to stalled polypeptides. If not degraded by the ribosome-associated quality control (RQC), CAT-tailed stalled polypeptides form aggregates. How the CAT tail, a low-complexity region composed of alanine and threonine, drives protein aggregation remains unknown. In this study, we demonstrate that C-terminal polythreonine or threonine-enriched tails form detergent-resistant aggregates. These aggregates exhibit a robust seeding effect on shorter tails with lower threonine content, elucidating how heterogeneous CAT tails co-aggregate. Polythreonine aggregates sequester molecular chaperones, disturbing proteostasis and provoking the heat shock response. Furthermore, polythreonine cross-seeds detergent-resistant polyserine aggregation, indicating structural similarity between the two aggregates. This study identifies polythreonine and polyserine as a distinct group of aggregation-prone protein motifs.

Mono-uridylation of pre-microRNA as a key step in the biogenesis of group II let-7 microRNAs.

RNase III Drosha initiates microRNA (miRNA) maturation by cleaving a primary miRNA transcript and releasing a pre-miRNA with a 2 nt 3' overhang. Dicer recognizes the 2 nt 3' overhang structure to selectively process pre-miRNAs. Here, we find that, unlike prototypic pre-miRNAs (group I), group II pre-miRNAs acquire a shorter (1 nt) 3' overhang from Drosha processing and therefore require a 3'-end mono-uridylation for Dicer processing. The majority of let-7 and miR-105 belong to group II. We identify TUT7/ZCCHC6, TUT4/ZCCHC11, and TUT2/PAPD4/GLD2 as the terminal uridylyl transferases responsible for pre-miRNA mono-uridylation. The TUTs act specifically on dsRNAs with a 1 nt 3' overhang, thereby creating a 2 nt 3' overhang. Depletion of TUTs reduces let-7 levels and disrupts let-7 function. Although the let-7 suppressor, Lin28, induces inhibitory oligo-uridylation in embryonic stem cells, mono-uridylation occurs in somatic cells lacking Lin28 to promote let-7 biogenesis. Our study reveals functional duality of uridylation and introduces TUT7/4/2 as components of the miRNA biogenesis pathway.

TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation.

As key regulators in cellular functions, microRNAs (miRNAs) themselves need to be tightly controlled. Lin28, a pluripotency factor, was reported to downregulate let-7 miRNA by inducing uridylation of let-7 precursor (pre-let-7). But the enzyme responsible for the uridylation remained unknown. Here we identify a noncanonical poly (A) polymerase, TUTase4 (TUT4), as the uridylyl transferase for pre-let-7. Lin28 recruits TUT4 to pre-let-7 by recognizing a tetra-nucleotide sequence motif (GGAG) in the terminal loop. TUT4 in turn adds an oligouridine tail to the pre-let-7, which blocks Dicer processing. Other miRNAs with the same sequence motif (miR-107, -143, and -200c) are regulated through the same mechanism. Knockdown of TUT4 and Lin28 reduces the level of stem cell markers, suggesting that they are required for stem cell maintenance. This study uncovers the role of TUT4 and Lin28 as specific suppressors of miRNA biogenesis, which has implications for stem cell research and cancer biology.

Physical activity, quality of life and parenting stress in children with cerebral palsy.

BACKGROUND: Children with cerebral palsy (CP) are less physically active than their typically developing peers. The effects of decreased physical activity on children's quality of life (QOL) or caregiver's lives are not well understood. This study aimed to investigate the association between physical activity, QOL, and parenting stress in children with CP. METHODS: A prospective cross-sectional study was done in children with CP. Daily physical activity was measured over 7 days using an accelerometer (ActiGraph™). Caregivers completed the Child Health Questionnaire - Parent Form 50 and Parenting Stress Index - Short Form. Multiple regression analysis was used. RESULTS: In total, data from 65 children with Gross Motor Function Classification System (GMFCS) levels I-V, aged 4-13 years, were analyzed. Non-ambulatory (GMFCS IV-V) children had significantly lower activity counts and moderate to vigorous physical activity (MVPA) in comparison with ambulatory (GMFCS I-II) and marginally ambulatory (GMFCS III) children. The ambulatory group had better physical QOL than the non-ambulatory group. Caregivers of the non-ambulatory or marginally ambulatory children with CP reported higher parenting stress levels than those of the ambulatory group. Time spent in MVPA and activity counts were positively associated with physical QOL in children with CP. Low activity counts and low amounts of MVPA of children with CP were significant predictors of high parenting stress. CONCLUSIONS: Physical activity in children with CP is associated with children's QOL and parenting stress. These results suggest that clinicians should conduct physical activity assessment and counseling to promote physical activity.

The Long-Term Functional Effect of Thrombectomy on Patients with Middle Cerebral Artery Occlusion Who Exhibit Moderate to Severe Disability.

Background and Objectives: Endovascular thrombectomy (EVT is an emerging gold standard treatment for acute cerebral infarction and may allow functional improvement after subacute cerebral infarction. However, the long-term functional benefits of EVT in patients with moderate to severe disability remain unclear. We investigated the effects of EVT on the activities of daily living (ADL), handicap, gait, and eating in patients with middle cerebral artery (MCA) occlusion who exhibited moderate to severe disability (score of 3-5 on the modified Rankin scale (mRS)) due to stroke, up to six months after onset. Materials and Methods: This retrospective longitudinal case-control study assessed 45 patients with MCA occlusion who exhibited moderate to severe disability (mRS score ≥ 3): 15 underwent EVT and 30 served as controls. Clinical assessments were conducted at two weeks (12-16 days), four weeks (26-30 days), and six months (180-210 days) after stroke onset. Functional assessments comprised the Korean version of the modified Barthel index (MBI), mRS, functional ambulation category (FAC), and dysphagia outcome severity scale (DOSS) to assess disability, handicap, gait, and eating. Results: The MBI, mRS, FAC, and DOSS scores all improved significantly (all p < 0.05) in the EVT group, compared to the controls. Conclusions: EVT has favorable effects on performing routine ADL, the handicap itself, walking, and eating. Therefore, EVT is recommended for patients with acute MCA occlusion, including those with severe disability at the initial assessment.

Profiling the Phytochemicals of Orostachys margaritifolia: Biological Activities, LC-ESI/MS, and HPLC Analyses.

Orostachys margaritifolia Y. N. Lee (OMY) is an endemic Korean plant in the family Crassulaceae that is known to contain a variety of bioactive compounds. To assess the physiological activities of an OMY ethanol extract, ABTS+ and DPPH radical scavenging assays and a nitric oxide (NO) inhibition assay were conducted. The phytochemical makeup of the extract was profiled via liquid chromatography-mass spectrometry (LC-ESI/MS) and high-performance liquid chromatography with a photodiode array detector (HPLC/PDA). The OMY extract was found to have weaker ABTS+ and DPPH radical scavenging activities than the control group (green tea). In the NO inhibition assay, the OMY extract induced a significant increase in macrophage cell viability but showed a lower NO inhibitory activity than l-NAME, producing an IC50 value of 202.6 µg/mL. The LC-ESI/MS and HPLC/PDA analyses identified isoquercitrin and astragalin in the OMY extract, quantifying their contents at 3.74 mg/g and 3.19 mg/g, respectively. The study revealed possibilities for the utilization of OMY as a future source of drugs for alleviating inflammation and diseases related to reactive oxygen species.

Performance of Activities of Daily Living in Typically Developing Children in Korea: Normative Value of K-MBI.

OBJECTIVE: To determine the normative values of the Korean version of the Modified Barthel Index (K-MBI) score for typically developing children in Korea and assess its suitability for use in children. METHODS: Rehabilitation physicians and occupational therapists with children were invited through an online platform to participate in a survey assessing their children's performance of activity of daily living (ADL) using the K-MBI. The questionnaire encompassed queries on sociodemographic information of children and the assessment criteria outlined in the K-MBI. The standardized K-MBI scores by age were estimated using the nonlinear least squares method. RESULTS: The analysis incorporated responses from a total of 206 individuals. K-MBI total scores showed a rapid increase over the first 8 years of life, with 99% of children achieving a score of 90 or higher by age 8. Mobility scores exhibited a swift increase during early childhood, surpassing 90% of the maximum score at 3 years of age and nearing 100% at 7 years of age. In contrast, self-care scores demonstrated a more gradual advancement, achieving approximately 100% of the maximum score by the age of 10 years. CONCLUSION: Age-specific normative values for K-MBI scores of typically developing children were established, which can be used as a reference in clinical care. While the K-MBI captured the overall trajectory of children's ADL development, it did not discern subtle differences across various developmental stages. There is a need for the development of more refined assessment tools tailored specifically to children.

Isolated Acute Dysphagia as a Probable Rare Presentation of Guillain-Barré Syndrome with Complete Recovery: A Case Report.

Dysphagia is prevalent among the elderly and can lead to serious complications, often manifesting as a clinical symptom of various neurological or muscular pathologies, including Guillain-Barré Syndrome (GBS). GBS is an acute immune-mediated polyradiculoneuropathy, and dysphagia may arise during its course due to cranial nerve involvement. In rare GBS variants, dysphagia may present as the initial or sole clinical manifestation, posing diagnostic challenges. In this study, we present the case of an elderly female patient with dysphagia, eventually diagnosed with an atypical variant of GBS. Initially, the patient required nasogastric tube feeding; however, complete recovery was achieved through immunotherapy. This case underscores the importance of clinicians conducting thorough evaluations of factors influencing the swallowing mechanism and remaining vigilant about identifying uncommon causative factors. Such approaches enable the implementation of effective disease-modifying therapies, potentially leading to the resolution of dysphagic symptoms.

Estimation of the muscle force by perineural intramuscular electrical stimulation in healthy volunteers.

The present study aimed to evaluate the elbow flexor force induced by perineural intramuscular stimulation compared with surface electrical stimulation (ES) and maximal voluntary contraction. Thirty nondominant arms of healthy volunteers were evaluated. Isometric elbow flexion force was evaluated using a surface electrode stimulation at the biceps brachii muscle, a perineural intramuscular stimulation around the musculocutaneous nerve, and maximum voluntary contraction. The elbow flexion force was measured at the wrist volar area in a 90° elbow flexion posture, fixed with a rigid elbow orthosis. Pain and discomfort associated with ES were evaluated using a numeric rating scale. The mean maximum elbow flexion force was 16.6 ±â€…4.1 kgf via voluntary contraction. The mean elbow flexion force by ES was 2.9 ±â€…2.0 kgf, stimulation intensity was 24.8 ±â€…5.5 mA, and the numeric rating scale was 5.0 ±â€…2.5 via surface electrode stimulation and 3.1 ±â€…2.0 kgf, 5.0 mA, and 3.8 ±â€…1.9 via perineural stimulation, respectively. ES provides 16% to 18% of the maximal voluntary contraction force in elbow flexion, which corresponds to a fair grade of muscle force. Perineural intramuscular stimulation can generate an equivocal contraction force with less discomfort in elbow flexion than surface electrode stimulation.

Electric field simulation and appropriate electrode positioning for optimized transcranial direct current stimulation of stroke patients: an in Silico model.

Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.

Sarcopenia Diagnostic Technique Based on Artificial Intelligence Using Bio-signal of Neuromuscular System: A Proof-of-Concept Study.

In this paper, we propose an artificial intelligence (AI)-based sarcopenia diagnostic technique for stroke patients utilizing bio-signals from the neuromuscular system. Handgrip, skeletal muscle mass index, and gait speed are prerequisite components for sarcopenia diagnoses. However, measurement of these parameters is often challenging for most hemiplegic stroke patients. For these reasons, there is an imperative need to develop a sarcopenia diagnostic technique that requires minimal volitional participation but nevertheless still assesses the muscle changes related to sarcopenia. The proposed AI diagnostic technique collects motor unit responses from stroke patients in a resting state via stimulated muscle contraction signals (SMCSs) recorded from surface electromyography while applying electrical stimulation to the muscle. For this study, we extracted features from SMCS collected from stroke patients and trained our AI model for sarcopenia diagnosis. We validated the performance of the trained AI models for each gender against other diagnostic parameters. The accuracy of the AI sarcopenia model was 96%, and 95% for male and females, respectively. Through these results, we were able to provide preliminary proof that SMCS could be a potential surrogate biomarker to reflect sarcopenia in stroke patients.

Feasibility of Sarcopenia Diagnosis Using Stimulated Muscle Contraction Signal in Hemiplegic Stroke Patients.

Sarcopenia, a condition characterized by muscle weakness and mass loss, poses significant risks of accidents and complications. Traditional diagnostic methods often rely on physical function measurements like handgrip strength which can be challenging for affected patients, including those with stroke. To address these challenges, we propose a novel sarcopenia diagnosis model utilizing stimulated muscle contraction signals captured via wearable devices. Our approach achieved impressive results, with an accuracy of 93% and 100% in sarcopenia classification for male and female stroke patients, respectively. These findings underscore the significance of our method in diagnosing sarcopenia among stroke patients, offering a non-invasive and accessible solution.

An Exercise Prescription for Patients with Stroke and Sarcopenia Based on the Modified Delphi Study.

BACKGROUND: We aimed to develop a consensus on the need for and priorities of exercise to treat preexisting sarcopenia with hemiplegic stroke. METHODS: A modified three-round Delphi study was conducted. The panelists responded to the questionnaire on a 7-point Likert scale. Responses were returned with descriptive statistics in the next round. Consensus was defined as >75% agreement (score of 5-7) with a median > 5. The percentage of strong agreement (score of 6-7) and Kendall's coefficient of concordance were calculated to demonstrate a more refined interpretation of the consensus. RESULTS: Fifteen panelists contributed to all rounds. The need for exercise was demonstrated. The consensus was reached on 53 of 58 items in the first round and all items in the second and final rounds. The percentage of strong agreement was high for all but eight items. CONCLUSIONS: This study is the first Delphi study to investigate the need for and priorities of exercise for treating preexisting sarcopenia in stroke hemiplegia. We present a standard recommendation including 57 priorities and a strong recommendation including 49 priorities. The eight items that were excluded reflected factors that are less important to hemiplegic patients with poor balance, cognitive decline, or mental vulnerability.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

The integrity of thalamo-dorsolateral prefrontal cortex tract: a key factor in residual consciousness in disorders of consciousness patients.

Background: The mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC. Methods: This retrospective case-control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging. Results: Significant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score. Conclusion: The integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC.

Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson's disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function. METHODS: This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging. DISCUSSION: The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD. TRIAL REGISTRATION: ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.

Structural Integrity of the Cerebellar Outflow Tract Predicts Long-Term Motor Function After Middle Cerebral Artery Ischemic Stroke.

BACKGROUND: The cerebellum plays a crucial role in functional movement by influencing sensorimotor coordination and learning. However, the effects of cortico-cerebellar connectivity on the recovery of upper extremity motor function after stroke have not been investigated. We hypothesized that the integrity of the cortico-cerebellar connections would be reduced in patients with a subacute middle cerebral artery (MCA) stroke, and that this reduction may help to predict chronic upper extremity motor function. METHODS: We retrospectively analyzed the diffusion-tensor imaging of 25 patients with a subacute MCA stroke (mean age: 62.2 ± 2.7 years; 14 females) and 25 age- and sex-matched healthy controls. We evaluated the microstructural integrity of the corticospinal tract (CST), dentatothalamocortical tract (DTCT), and corticopontocerebellar tract (CPCT). Furthermore, we created linear regression models to predict chronic upper extremity motor function based on the structural integrity of each tract. RESULTS: In stroke patients, the affected DTCT and CST showed significantly impaired structural integrity compared to unaffected tracts and the tracts in controls. When all models were compared, the model that used the fractional anisotropy (FA) asymmetry indices of CST and DTCT as independent variables best predicted chronic upper extremity motor function (R2 = .506, P = .001). The extent of structural integrity of the CPCT did not significantly differ between hemispheres or groups and was not predictive of motor function. CONCLUSIONS: We found evidence that microstructural integrity of the DTCT in the subacute phase of an MCA stroke helped to predict chronic upper extremity motor function, independent of CST status.

Safety and therapeutic effects of personalized transcranial direct current stimulation based on electrical field simulation for prolonged disorders of consciousness: study protocol for a multi-center, double-blind, randomized controlled trial.

Background: Disorders of consciousness (DOC) resulting from acquired brain injury (ABI) increase the mortality rate of patients, complicate rehabilitation, and increase the physical and economic burden that DOC imposes on patients and their families. Thus, treatment to promote early awakening from DOC is vital. Transcranial direct current stimulation (tDCS) has shown great potential for promoting neuro-electrochemical activity. However, previous tDCS studies did not consider structural damage or head and brain lesions, so the applicability of the results to all DOC patients was limited. In this study, to establish a patient-specific tDCS treatment plan considering the brain lesions of and damage sustained by DOC patients, we considered the electric field calculated by a the "finite electric" three-dimensional brain model based on magnetic resonance images. This protocol was developed to aid tDCS treatment of actual patients, and to verify its safety and effectiveness. Methods/design: Twenty-four patients with DOC after ABI will be enrolled in this cross-over trial. All participants will receive typical rehabilitation combined with sham tDCS and typical rehabilitation plus personalized tDCS (P-tDCS). Each interventional period will last 2 weeks (30 min/day, 5 days/week). The primary outcome [score on the Korean version of the Coma Recovery Scale-Revised (K-CRS-R)] will be assessed at baseline and the end of the first day of the intervention. Secondary outcomes (K-CRS-R at 1 week and 2 weeks after experimental session and quantitative EEG changes quantitative electroencephalography changes) will be measured at baseline and the end of week 4. Adverse events will be recorded during each treatment session. Discussion: For patients with neurological disorders, tDCS has served as a painless, non-invasive, easily applied, and effective therapy for several decades, and there is some evidence that it can improve the level of consciousness of patients with DOC. However, variability in the effects on consciousness among subjects have been reported and personalized strategies are lacking. This protocol is for a randomized controlled trial designed to validate the effectiveness and safety of P-tDCS combined with typical rehabilitation for DOC. Clinical trial registration: https://cris.nih.go.kr, identifier KCT0007157.

Factors Influencing the Progression and Direction of Scoliosis in Children with Neurological Disorders.

(1) Background: scoliosis is highly prevalent in children with neurological disorders, however, studies predicting the progression and affecting the direction of scoliosis have been insufficient. We investigated the factors associated with the progression and direction of scoliosis in children with neurological disorders. (2) Method: retrospectively, 518 whole spine radiographs from 116 patients were used for analysis. Factors affecting the progression of scoliosis over time were analyzed using linear mixed-effects model. Factors associated with the apex direction of the scoliosis were analyzed. (3) Results: pelvic obliquity (PO) ≥ 2.5°, gross motor function classification system level V, vertebral rotation, and female sex significantly affect the progression of scoliosis (p = 0.04, <0.001, <0.001, 0.005, respectively). The higher side of PO and the apex side of scoliosis were interrelated (χ² = 14.58, p < 0.001), but the asymmetrical neurological upper extremity involvement was not. (4) Conclusions: severely impaired gross motor function, PO, vertebral rotation, and female sex were significantly related to the progression of scoliosis. The higher side of PO was opposite to the apex side of scoliosis. By identifying the factors that influence the progression of scoliosis, patients at high risk could be more actively intervened to minimize the severe complications.

Clinical Course of Dysphagia in Patients with Nemaline Myopathy.

Nemaline myopathy (NM) is a rare congenital myopathy, a group of disorders that are clinically and genetically heterogeneous. Infants and children with NM often suffer from recurrent pulmonary infections and swallowing difficulty, leading to malnutrition. However, knowledge about the clinical course and prognosis of dysphagia is limited. In this study, we reported the clinical course of two NM patients suffering from dysphagia. Although tube feeding was required for several months after birth, it was eventually possible to obtain sufficient nutrition with an oral diet. Therefore, dysphagia rehabilitation therapy through a series of evaluations should be considered even in children with severe oral motor dysfunction. Through these cases, physicians should be convinced that the symptoms of dysphagia in children with NM can be improved and be able to encourage their parents by explaining this progress. They have the potential to show improvements in swallowing function and will finally be able to take food slowly but fully orally.